Adjuvant chemotherapy with 5-fluorouracil (5-FU) and leucovorin (LV) has proven to be beneficial in the management of patients with Dukes' B and C colon cancer (1). However, there remains a need for further improvement in the efficacy of this therapy without additive excessive toxicity. The concept of combining adjuvant chemotherapy with FU-LV and radioimmunotherapy (RAIT) in colon cancer is especially attractive because of the additive and potentially synergistic anti-tumor effects of both modalities. The combination of RAIT and chemotherapy may, however, result in increased hematological toxicity, although 5-FU usually causes mild to moderate nyelosuppression. The dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of combined RAIT and 5-FU-LV has therefore, to be established experimentally, before it can be used as a potential adjuvant therapy for colon cancer patients. While the ultimate intent of our proposed research is to combine RAIT with 5-FU-LV as a potential adjuvant therapy in patients with resected high-risk Dukes' B and C colon cancer, it is prudent that studies of combined RAIT and chemotherapy with 5- FU-LV first be performed in patients with established disease to gather critically important data, primarily on the toxicity of this combination, before it can be considered as an adjuvant therapy program. We intend, therefore, to conduct a phase-I trial of combined 5-FU-LV and RAIT with a CDR-grafted (humanized) 131I-MN-14 (hMN-14) second-generation, high affinity anti-CEA MAb. The use of the humanized form of the MAb (hMN-14) will allow the administration of multiple MAb doses in combination of chemotherapy, without the fear of HAMA associated with the use of murine MAbs. The proposed trial is designed with the objectives of both determining the maximum-tolerated single course and number of RAIT courses of 131I-hMN-14 that can be combined with 5-FU-LV without the need for autologous hematopoietic stem cell rescue (AHSCR).